1. Islets of Langerhans were isolated from Lewis rats and transplanted to the same descent rats at either subcutaneous tissue (SCT), liver via the portal vein or subnephrocapsular space (SNCS). Up to 4 weeks after transplantation, insulin staining showed viable islets at the liver and SNCS but not at SCT.2. Normal rat pancreas, islets of Langerhans immediately after isolation, and transplanted islets either at the liver or SNCS were immunostained for vascular endothelial growth factor (VEGF) after trypsin treatment. Islets in the normal pancreas and immediately after isolation were positively stained but those at transplantation (Tx) sites tended to be VEGF-negative. On the other hand, VEGF-staining after microwave treatment showed positive results even in the islets at Tx sites, suggesting that VEGF still exists after Tx. A marker for blood vassels, factor VIII-related antigen (vWF), and specific marker for neogeneic vessels, platelet endothelial cell adhesion molecule-1 (PECAM-1/CD-31) were similarly immunostained. PECAM-1 was not stained in the islets of normal pancreas but became positively stained in those at Tx sites, whereas vWF was stained in normal and transplanted islets.3. Effects of an anti-neovascularization agent, TNP-470, were examined in islet-transplanted streptozotocin (STZ)-diabetic rats. Administered of TNP-470 did not altered blood glucose levels either at fed state or during oral glucose tolerance test. However, it abolished plasma insulin increase in response to oral glucose challenge, which was observed in normal rats and islet-transplanted STZ-rats without TNP-470 treatment. Histological examination revealed vessel-like tubular structures, which lack PECAM-1-positive endothelial layer.These results suggest that neovascularization can be evoked from transplanted islets and that neovascularization-promoting treatment may improve the function of transplanted islets.